Key points
What is known
– Congenital diaphragmatic hernia (CDH) is a life-threatening anomaly.
– Pulmonary hypoplasia, pulmonary hypertension, and cardiac dysfunction are the main determinants of morbidity and mortality.
– The management of CDH remains challenging and there is no universally accepted treatment protocol.
What is added
– This article provides a concise overview of current international treatment guidelines for CDH.
– It summarizes the most relevant prenatal prognostic indices, offering neonatologists practical tools to assess disease severity.
– By compiling and simplifying complex international recommendations, this article serves as a valuable resource for clinicians managing CDH in the neonatal period.
Introduction
Congenital diaphragmatic hernia (CDH) is a rare but serious developmental anomaly, occurring in approximately one in every 3000 live births.1–4 Characterized by a defect in the diaphragm that allows abdominal organs to herniate into the thoracic cavity, CDH is associated with significant pulmonary hypoplasia, CDH-associated pulmonary hypertension (CDH-PH), and cardiac dysfunction, which are the main determinants of neonatal morbidity and mortality.5,6
Over the past two decades, advances in neonatal intensive care, prenatal diagnosis, and respiratory support strategies have contributed to a gradual improvement in survival rates.7 Once considered uniformly fatal, the survival of infants with CDH now exceeds 70% in specialized centers.4,7 However, this progress has not been consistent across all healthcare settings.4
Despite improved outcomes, the medical management of CDH remains highly variable.8 There is no universally accepted protocol, and significant discrepancies persist among international guidelines regarding the timing of interventions, use of pulmonary vasodilators, ventilation strategies, and criteria for extracorporeal life support (ECLS).9 This lack of standardization poses challenges not only for clinical decision-making but also for comparing outcomes across centers and conducting robust research.10
This article aims to review the prognostic factors and the current medical management of CDH from a neonatologist’s perspective, highlighting key areas of consensus, ongoing controversies, and opportunities for the standardization of care.
Methods
To prepare this article, the most relevant publications on the medical management of CDH from the last ten years, up to July 1, 2025, were reviewed using the PubMed database. Some older articles referenced in the analyzed papers were also reviewed and are cited in this review. The search terms used were: congenital diaphragmatic hernia, treatment, prenatal diagnosis, prognostic, fetal endoscopic tracheal occlusion, cardiac, delivery, resuscitation, treatment, management, ventilation, sedation, analgesia, pulmonary hypertension (PH), hemodynamic support, vasoactive, vasodilator, surgical repair, extracorporeal membrane oxygenation (ECMO), outcomes, malnutrition, feeding difficulties, gastroesophageal reflux, chronic lung disease, and mortality.
Development
Prognostic implications of the diaphragmatic defect type
The majority of CDH are Bochdalek hernias, which occur posterolaterally and account for approximately 85-90% of cases.11 These defects arise due to the incomplete closure of the pleuroperitoneal canals during fetal development, predominantly (80-85% of cases) affecting the left hemidiaphragm.11 The anatomical severity of the diaphragmatic defect has been standardized using the CDH Study Group classification, which categorizes defects as follows: Type A: small, isolated defect with intact diaphragmatic musculature surrounding the hernia; suitable for primary repair without tension; Type B: moderate-sized defect with partial posterolateral muscular discontinuity; less than 50% of the chest wall is devoid of diaphragm; generally amenable to primary repair but may require reinforcement; Type C: large defect with minimal residual diaphragmatic tissue; more than 50% of the chest wall lacks a diaphragm; primary repair is typically not feasible and requires prosthetic patch reconstruction; Type D: near-total or complete agenesis of the hemidiaphragm; requires extensive patch repair and is often associated with severe PH and malrotation.12
There is a well-established correlation between the defect type and postnatal outcomes. Types A and B are associated with favorable prognoses, lower surgical complexity, and a reduced incidence of postnatal complications. These patients typically exhibit better pulmonary function, a shorter duration of mechanical ventilation, and a decreased need for ECLS.13 Conversely, Types C and D represent severe phenotypes, frequently requiring prosthetic repair, and are associated with significant morbidity and mortality. These neonates exhibit increased rates of CDH-PH, prolonged respiratory support, feeding difficulties, and higher rates of recurrence. Important long-term sequelae, including chronic lung disease (CLD), may occur in patients with CDH.14,15
Herniation of the abdominal contents leads to persistent hypoplasia of the ipsilateral lung, while the resulting secondary mass effect contributes to hypoplasia of the contralateral lung.5 These anatomical changes impact lung mechanics by reducing lung volumes and causing smooth muscle dysregulation, which increases airway resistance. Additionally, the pulmonary vasculature is affected, resulting in a decreased cross-sectional area of the pulmonary vascular bed and thickening of the adventitia and media, leading to elevated pulmonary vascular resistance (PVR). Due to the chronic nature of these changes, the elevated PVR becomes fixed and less responsive to vasodilators such as inhaled nitric oxide (iNO). Over time, this sustained increase in PVR may result in right heart strain and right ventricular (RV) hypertrophy, particularly after the patent foramen ovale (FO) and ductus arteriosus (DA) have closed.5
Accurate intraoperative classification of the diaphragmatic defect provides essential prognostic information and should be systematically documented.16 Additionally, advances in prenatal imaging, particularly fetal magnetic resonance imaging (MRI), allow for a more precise antenatal estimation of the defect size and associated lung volumes, improving risk stratification and perinatal management planning.16
Beyond the size of the diaphragmatic defect, estimated indirectly through ultrasound (US) and MRI-based assessments of fetal lung volume, and the extent of visceral herniation, several other factors can impact both the immediate and long-term prognosis of CDH. These include the timing of prenatal diagnosis, gestational age at detection, the side of the defect (laterality), the presence of additional structural or genetic anomalies, gestational age at delivery, and the experience of the delivery center in managing neonates with CDH.16
Prenatal issues
The prenatal diagnosis of CDH plays a crucial role in planning perinatal care and assessing prognosis16. In high-income countries, the integration of US into routine prenatal care has markedly improved the detection rates of CDH, rising from approximately 15% to over 60%, which has likely contributed to improved postnatal survival outcomes.7,17,18
CDH is typically diagnosed during the second-trimester routine obstetric anatomy scan (18-24 weeks of gestation). Sonographic signs include the presence of abdominal organs (e.g., stomach, intestines or liver) within the thoracic cavity, mediastinal shift, and an absent or small stomach bubble in the abdomen16. Left-sided hernias, the most common form, are usually easier to detect due to the displacement of the heart and visualization of the stomach in the thorax.16,19 Fetal MRI may be used to complement US findings and provide a detailed assessment of lung volumes, liver herniation, and the presence of other congenital anomalies, all important prognostic factors.20 Additionally, MRI images are independent of maternal body habitus, fetal position, or abnormalities in the amniotic fluid.20
Approximately 30-50% of CDH are “non-isolated” or “syndromic”.21 A comprehensive morphological evaluation, including an assessment of the cardiac structure and function, as well as genetic testing, should be conducted in all pregnancies with fetuses diagnosed with CDH.22 There is no genetic panel for CDH.23 Invasive genetic testing with chromosomal microarray analysis should be offered in cases of isolated CDH, whereas more targeted mutation identification or expanded genomic analyses (e.g., exome sequencing) are likely to further improve the diagnostic yield in “syndromic” or “non-isolated” cases.23
Prognostic indicators
Several prenatal indices have been developed to estimate the severity of CDH and guide clinical decision-making (Table 1). The lung-to-head ratio (LHR) is measured via US and represents the area of the contralateral lung divided by the head circumference. An observed-to-expected (o/e) LHR is often used to standardize measurements across gestational ages. The o/e LHR should be measured with the trace method between 22 and 32 weeks of gestational age in experienced centers. Severe pulmonary hypoplasia is predicted by an o/e LHR of ≤ 25% in left-sided CDH and ≤ 50% for right-sided CDH, with an estimated survival rate of ≤ 30%.24–28 In cases of left-sided CDH, moderate pulmonary hypoplasia is defined by an o/e LHR ranging from 26 to 34%.28
Table 1. Prenatal imaging parameters and their thresholds for predicting mortality in cases of congenital diaphragmatic hernia that are managed expectantly16
| Prenatal parameter | Cut-off | Mortality (%) |
|---|---|---|
| o/e LHR (on US) Left CDH Right CDH |
< 25% < 50% |
50-70 80 |
| Liver herniation (on MRI) | > 21% | 20-52.4 |
| Stomach herniation (on US) | Grade IV/Retrocardiac | 61 |
| o/e TFLV (on MRI) | < 25% < 35% |
75-100 30-75 |
| o/e TFLV with liver herniation (on MRI) | < 35% with liver “up” | 75 |
CDH: congenital diaphragmatic hernia; o/e LHR: observed-to-expected lung/head ratio; MRI: magnetic resonance image; o/e TFLV: observed-to-expected total fetal lung volume; US: ultrasound.
The presence of the liver in the thoracic cavity (“liver up”) is considered a negative prognostic factor, as it reflects a larger diaphragmatic defect and more severe lung compression. Intrathoracic liver herniation can be challenging to detect on US. Consequently, stomach position classification has been proposed as a surrogate marker and has been shown to correlate with neonatal mortality and morbidity.29–33 The position of the stomach is graded I – IV (I: intra-abdominal, II: anterior left chest, III: mid-to-posterior left chest, and IV: retrocardiac) based on the degree of thoracic herniation; a higher grade indicates more severe herniation and a worse prognosis.31 The o/e total fetal lung volume (o/e TFLV) measured by fetal MRI is another reliable marker.28 An o/e TFLV < 35% with liver herniation is linked to a higher mortality rate.28 The optimal timing for MRI appears to be around 26 weeks, as performing it earlier may result in inaccurate measurements. When combined, the o/e TFLV and liver herniation indicators provide improved predictive value for mortality and the need for ECLS.34
While MRI offers advantages for prenatal prognostication, US is likely to remain the primary tool due to its broad accessibility. Ideally, both imaging modalities should be used complementarily, especially in high-risk fetuses.28 MRI for the assessment of o/e TFLV and liver herniation should be considered in all fetuses with CDH, and it is strongly recommended in fetuses with severe or moderate CDH by o/e LHR.28
During pregnancy, multidisciplinary counselling is provided, and various management options are discussed, including expectant management, fetoscopic endoluminal tracheal occlusion (FETO), pregnancy termination, and palliative care (in cases that are syndromic, severe, or bilateral).35
Fetal endoscopic tracheal occlusion eligibility
For severe and moderately severe cases of CDH, the use of FETO should be considered a treatment option.28 Eligibility often depends on prognostic indicators like o/e TFLV and the liver herniation status. A systematic review and meta-analysis including a total of 1187 CDH fetuses from 20 studies demonstrated that FETO is associated with a reduction in mortality, the rate of CDH-PH, and ECMO usage in severe CDH, while it reduces only the risk of mortality in moderate CDH.36 Although FETO increases the risk of late prematurity, it does not result in extreme prematurity.36
The decision to proceed with FETO should be individualized, based on detailed imaging, multidisciplinary evaluation, and careful counselling of the parents regarding the risks and benefits.28
Cardiac parameters
Fetuses with CDH are at risk of cardiac chamber abnormalities, particularly left ventricular (LV) hypoplasia, leading to biventricular dysfunction after birth.37,38 Emerging evidence suggests that cardiac dysfunction plays a key role in CDH pathophysiology. It remains uncertain whether these morphological changes stem from a primary embryological defect or are secondary to altered fetal hemodynamics and cardiac compression due to visceral herniation.16 Postnatal ventricular imbalance and dysfunction are linked to higher mortality and an increased need for ECLS, although fetal cardiac size does not consistently predict outcomes. Further studies are needed to identify fetal cardiac parameters that may improve the prediction of neonatal outcomes in prenatally diagnosed CDH.16
Delivery
The delivery of a fetus with CDH should occur in a high-volume tertiary center equipped with a multidisciplinary team experienced in neonatal intensive care, pediatric surgery, and ECLS, if needed.39 The mode of delivery should be determined on usual obstetric grounds and should be considered between 38 and 39 weeks of gestation, as earlier delivery has not been shown to improve outcomes and may be associated with an increased risk of prematurity.40 In the case of an early birth prior to 34 weeks of gestation, antenatal steroids should be given.41 Planned delivery at term allows for stabilization of the newborn prior to surgical repair, which is associated with improved survival and reduced morbidity.9,41 Whenever possible, delivery should be scheduled for an early weekday during daytime hours, ensuring the optimal availability of experienced personnel and allowing for timely planning of CDH repair within the first week of life.9 Obstetric management should prioritize achieving a normal umbilical cord arterial pH at birth in order to minimize the degree of respiratory acidosis during the neonatal transition.9
Management of a neonate with congenital diaphragmatic hernia
Neonates with CDH often present with respiratory distress immediately after birth.42 The severity can vary depending on the degree of pulmonary hypoplasia and CDH-PH. Common clinical signs include tachypnea, nasal flaring, grunting, and cyanosis. On physical examination, breath sounds may be decreased or absent on the affected side, and heart sounds may be displaced due to mediastinal shift. The abdomen may appear scaphoid due to the herniation of abdominal contents into the thoracic cavity. In severe cases, the newborn may present with signs of cardiovascular instability, such as hypotension and poor perfusion. A prenatal diagnosis is common, but undiagnosed cases may first be identified based on postnatal clinical findings and confirmed by chest radiography.42 About 5% of CDH cases will present after 24 hours of age with mild tachypnoea, or even later with failure to thrive, recurrent chest infections, pleural effusions, or as an incidental finding on a chest X-ray.42
The management of neonates affected of CDH requires a multidisciplinary approach and highly specialized neonatal intensive care from birth.41 Neonatal CDH care focuses on three overlapping domains: pulmonary hypoplasia, CDH-PH, and biventricular cardiac dysfunction.9 Preoperative medical management involves stabilizing the infant’s oxygenation, hemodynamics, and acid-base balance, and providing nutritional support, beginning immediately in the delivery room.41 The severity of pulmonary and cardiac impairment determines the timing of surgery, which should be deferred until cardiac function and CDH-PH have improved.43–46
Delivery room stabilization and resuscitation
The initial management of CDH patients in the delivery room is a critical medical intervention that significantly impacts patient prognosis.47 The initial approach is based on the 2025 updated newborn life support guidelines from the European Resuscitation Council.48
Immediate postnatal care focuses on gentle stabilization rather than aggressive resuscitation. Bag-mask ventilation is contraindicated due to the risk of gastric insufflation and further compromise of lung function. Endotracheal intubation should be performed promptly after birth. A nasogastric or orogastric tube should be inserted to decompress the stomach and reduce thoracic compression. Chest compressions are rarely needed; instead, the focus is on achieving adequate oxygenation and ventilation while avoiding barotrauma. The delivery room management of a newborn with CDH is summarized in table 2.28,35,41,47,49–52
Table 2. Delivery room management of a newborn with congenital diaphragmatic hernia28,35,41,47,49–52
| Cord clamping | DCC is generally advocated in neonates, including those with CDH. In the case of critical CDH, where immediate resuscitation is required, healthcare providers may opt for a faster intervention over DCC. There is an ongoing trial (NCT04373902) aimed at investigating whether cord clamping after lung aeration in CDH, referred to as physiological-based cord clamping, could reduce the incidence of PH in the first 24 hours after birth. Additionally, the Congenital Hernia Intact Cord (CHIC) trial is a prospective, multicenter, open-label, randomized controlled trial designed to assess its primary endpoint in two groups (early and delayed cord clamping): the number of infants with an APGAR score < 4 at one minute or < 7 at five minutes. |
| Intubation | Avoid using positive-pressure mask ventilation as it may cause gastric distension and lung compression. After delivery, the infant should be intubated. In infants with a prenatal diagnosis and favorable prognostic indicators (e.g., left-sided defect, o/e LHR > 50%, and liver down), intubation may be avoided; however, even vigorous neonates with favorable prenatal predictors often require intubation for surgery and to avoid developing PH. Premedication should be given before intubation, if possible. Neuromuscular blocking agents should be avoided. The position of the ETT should be confirmed by end-tidal CO2 monitoring if there is no thorax expansion or improvement in SpO2. |
| Oxygen | Initiate resuscitation with an FiO2 below 1.0 (e.g., 0.30 if the liver is abdominal; 0.50 if the liver is intra-thoracic and in right-sided CDH), titrating up to 1.0, if adequate oxygenation is not achieved. FiO2 is titrated to achieve a pre-ductal oxygen saturation minimum goal of ≥ 85% by 10 min after birth. Saturation (SpO2) targets: pre-ductal between 85 and 95%; post-ductal saturation above 70%. To avoid hyperoxia, supplemental oxygen should be diminished when pre-ductal saturation exceeds 95%. NIRS cerebral oxygenation may supplement pulse oximetry and heart rate monitoring. |
| Gastric tube | Insert an orogastric or nasogastric tube (8F for < 34 weeks GA and 10F for > 34 weeks), with continuous or intermittent suction, for abdominal decompression. |
| Sedation | If the infant is agitated and/or fighting the ventilator, intranasal midazolam may be administered to achieve sedation prior to initiating an intravenous infusion. |
| Mechanical ventilation |
Conventional ventilation (e.g.,: SIPPV) PIP: start with 20 cmH2O and increase up to 25 cmH2O (avoiding pressure > 25). PEEP: 3-5 cmH2O. Frequency: 40-60/min. Inspiratory time: 0.3 seconds. Use volume targeted ventilation (tidal volume 4-6 mL/kg). Permissive hypercapnia: PaCO2 50-70 mmHg. Arterial pH: 7.25-7.35. |
| Vascular access | Umbilical venous catheter: may be needed in the event of advanced resuscitation. Consider obtaining a microarray from cord blood or from umbilical catheter, in isolated and non-syndromic cases. |
| Hemodynamic | Maintain mean arterial blood pressure above the lower limit of normal levels for the gestational age (maintaining 45 to 55 mmHg for term neonates). In the case of hypotension and/or poor tissue perfusion, one fluid bolus of 10-20 ml/kg NaCl 0.9% may be administered. |
CDH: congenital diaphragmatic hernia; CO2: carbon dioxide; DCC: delayed cord clamping; ETT: endotracheal tube; F: French; FiO2: fraction of inspired oxygen; GA: gestational age; NaCl: sodium chloride; NIRS: near-infrared spectroscopy; o/e LHR: observed-to-expected lung-to-head ratio; PaCO2: arterial partial pressure of carbon dioxide; PEEP: positive end expiratory pressure; PH: pulmonary hypertension; PIP: peak inspiratory pressure; SIPPV: synchronized positive pressure ventilation; SpO2: peripheral oxygen saturation.
Ventilation strategies
Permissive hypercapnia and “gentle ventilation” have been associated with improved survival rates in neonates with CDH.35,41,52–54 Lung-protective ventilation is the cornerstone of respiratory management. Caring for asymmetric lungs requires clinicians to find a delicate balance between atelectasis of the larger lung and hyperinflation of the smaller lung.9 The optimal initial ventilation strategy was explored in the VICI trial (NTR1310).55 Although the primary outcome (death/CLD at day 28) did not differ significantly between the two groups, it was found that infants initially ventilated with conventional mechanical ventilation required a significantly shorter duration of ventilation, had a lower need for iNO or sildenafil, needed less vasoactive medication, and were less likely to require ECMO than the group initially ventilated with high-frequency oscillatory ventilation (HFOV). The CDH EURO Consortium recommends conventional mechanical ventilation as the initial ventilation strategy.41
Conventional mechanical ventilation with low peak inspiratory pressures and permissive hypercapnia is preferred to minimize ventilator-induced lung injury. In cases where conventional ventilation is inadequate, rescue HFOV may be used. Oxygenation targets should be tailored to maintain pre-ductal SpO2 between 85-95%, avoiding both hypoxemia and hyperoxia. Table 3 provides a summary of the medical management for newborns with CDH from delivery room care, including ventilation strategies.8,9,28,35,41,47,49,56
Table 3. Management of a newborn with congenital diaphragmatic hernia in the Neonatal Intensive Care Unit8,9,28,35,41,47,49,52–56
| Ventilation strategies | Lung-protective ventilation is the cornerstone. Synchronized conventional mechanical ventilation is recommended as the initial strategy: SIPPV or SIMV. Use volume targeted ventilation (4-6 mL/kg). Try to maintain spontaneous respiration, avoiding over-sedation. Start with a ventilator rate of 40-60/min and an inspiratory time (iT) of 0.3 sec.; adjust the rate to maintain a PaCO2 of 40-65 mmHg and arterial pH of 7.25-7.40. PIP should not be higher than 25 cmH2O. If a PIP greater than 25 cmH2O is required to achieve the target PaCO2 and saturation levels, alternative treatment modalities, such as HFOV or ECMO, should be considered. If a persistent leak > 25% is present, consider upsizing the ETT. Use a PEEP of 3-5 cmH2O. If there are oxygenation issues and a chest X-ray shows collapse or underinflated lungs, consider a trial of higher PEEP. Chest X-ray: larger lung to an expansion of 8-9 ribs; the smaller lung ipsilateral to the hernia should not be visible on the pre-operative radiograph. HFOV can be used as rescue ventilation. When transitioning infants to HFOV, particularly term infants, have them well sedated and consider muscle relaxation. Commence at a MAP equal to that on conventional ventilation (11-17cmH2O). MAP should not exceed 17 cmH2O; Frequency of 6-8Hz with adjustments made based on gestational age. Use highest frequency that will allow for adequate gas exchange. Delta P of amplitude adjusted until chest oscillation is seen (usually 30-45 cmH2O). Obtain chest X-ray within one hour to watch for adequate lung inflation. Look at contralateral lung; 7-8 posterior ribs with a curved diaphragm. If chest X-ray shows > 9 posterior ribs and flattened diaphragm, reduce the MAP. |
| Surfactant | Usually not necessary nor indicated. In preterm infants ≤ 34 weeks GA, if the chest X-ray or lung ultrasound is suggestive of RDS, surfactant is indicated. |
| Oxygen | Pre-ductal saturation levels: between 85 and 95%. In individual cases, levels as low as 80% may be acceptable, provided that organ perfusion is adequate, as indicated by a pH > 7.2, lactate levels < 5 mmol/L, and urinary output > 1 mL/kg/h. Post-ductal saturations should remain above 70%. Persistent post-ductal saturations < 70% are indicative of PH and require intervention. Oxygen toxicity needs to be prevented; reduce FiO2 if the pre-ductal saturation is above 95%. FiO2 should be weaned or increased gradually, typically in 3% increments. Metabolic acidosis should be promptly corrected with sodium bicarbonate. Pre-ductal PaO2 should be kept > 30 mmHg, although PaO2 is not recommended to guide ventilator management; if the post-ductal PaO2 is < 40 mmHg, FiO2 should not be weaned. NIRS cerebral oxygenation may supplement pulse oximetry and heart rate monitoring; use normal reference ranges for NIRS values (55 to 85%). |
| Sedation | Judicious sedation is recommended. Deep sedation is contraindicated. Neuromuscular blockade can impair respiratory function, decrease lung compliance, and increase oxygenation indices and mortality. The main goals are to minimize stress and oxygen consumption, prevent patient-ventilator dyssynchrony, prevent abrupt movements that increase intrathoracic pressure, and maintain hemodynamic stability. Opioids such as morphine sulfate or fentanyl may be used. Morphine has a higher risk of hypotension and histamine release than fentanyl. Commence either morphine (5-10 mcg/kg/h) or fentanyl (0.5 at 3 mcg/kg/hour). Neonatal sedation scales (e.g., N-PASS or COMFORT) can guide sedation titration. If fentanyl perfusion is started, after the first 24-48 hours of life infants should be transitioned from fentanyl to morphine infusions to avoid the development of tachyphylaxis. A bolus of opioid may be required for interventions. A midazolam (20-60 mcg/kg/h) or dexmedetomidine (0.2-0.5 mcg/kg/h) infusion may be required for muscle relaxation. Midazolam may cause hypotension, especially when combined with opioids. Consider muscle relaxation (vecuronium 0.1-0.2 mg/kg IV bolus or rocuronium 0.15 mg/kg IV bolus) in severe cases of ventilator dyssynchrony despite optimization of ventilator settings and sedation. Infants should remain sedated until weaning from mechanical ventilation. Sedation plans should be regularly reassessed. |
| Bladder catheter | To monitor renal function and fluid balance; prevent urinary retention and associated discomfort; help manage abdominal pressure and ventilation complications; and facilitate nursing care by reducing the need for frequent handling. |
| Vascular access | Umbilical venous catheter (double-lumen) for fluids and medications for up to five days. An umbilical venous line may not be able to be placed, most likely secondary to an intra-thoracic liver. Peripherally inserted central catheter: should be placed to replace UVC. Right radial artery: allows PaO2 measurement and reflects the level of oxygen delivered to the brain. Umbilical arterial catheter: reflects the post-ductal saturation, but it may give a more secure longer-term arterial access. |
| Fluid management | Fluid intake restriction is recommended (60-80 mL/kg/day) to prevent pulmonary edema. Pre-operative and post-operative fluid status is crucial. It is important to monitor for signs of fluid overload (CVP persistently > 5 cmH2O; CVP trending up after fluid bolus; peripheral edema; and worsening respiratory function). If there are signs of fluid overload or pulmonary congestion, then: reduce sedation and muscle relaxation to allow some spontaneous movement; judicious use of diuretics; and consider fluid restriction. Diuretics may be used in selected cases. Diuretics should be considered in the case of persisting positive fluid balance: aim for a diuresis > 1 ml/kg/h. Parenteral nutrition should be initiated early (see Table 6). |
| Antibiotics | Use antibiotics based on risk factors for perinatal infection (e.g., ampicillin and gentamycin). Does not require empiric prophylactic antibiotic coverage. Cefazolin may be used for perioperative antibiotic prophylaxis. |
| Hemodynamic | Sedation, acid-base status, and lung recruitment should always be optimized. Early and regular echocardiographic assessment of cardiac function and pulmonary artery pressure can guide therapeutic decision-making. When the heart rate is within the normal range, urine output exceeds 1.0 ml/kg/h, lactate levels are below 3 mmol/L, and there are no other signs of inadequate tissue perfusion, the use of inotropic or vasopressor support is unnecessary. If symptoms of poor perfusion and/or BP below the normal level for GA occur and are associated with pre-ductal saturation below 80%, echocardiographic assessment should be performed. Mean BP maintained within normal limits. Historically, PH treatment involved aggressive vasoconstriction to raise systemic BP and promote left-to-right ductal shunting. However, this approach can be detrimental. Additionally, in patients with severe LV dysfunction (phenotype 3), excessive afterload can worsen LV function. Careful, targeted use of lower-dose systemic vasoconstrictors is now preferred to optimize blood pressure without causing harm. In the case of hypovolemia, fluid therapy (10-20 ml/kg NaCl 0.9%) may be given up to two times. Consider initiating inotropes if there is a minimal response to the fluid bolus and no signs of excessive fluid loss. If the echocardiogram reveals predominant RV dysfunction (usually associated with PH), agents to reduce PVR and enhance RV function such as iNO, milrinone, dobutamine, low-dose epinephrine, and PGE1, may need to be used. The use of prostaglandin E1 (PGE1) is recommended when a dilated and dysfunctional RV is present, accompanied by systemic or supra-systemic pulmonary arterial pressures and a restrictive PDA. If the echocardiogram reveals predominant LV dysfunction (usually with reduced cardiac output and systemic hypotension), myocardial function should be supported with low-dose epinephrine and/or dobutamine. Milrinone can also be used if needed, and it can be combined with epinephrine. PGE1 may be indicated in newborns whose circulation depends on a PDA, providing temporary support until inotropic support is effective. In the presence of systemic hypotension with preserved cardiac function, norepinephrine or vasopressin may be used. Frequent review of the volume status is required prior to and after commencing inotropes. An echocardiogram should be considered to evaluate cardiac function and filling before and after inotropes whenever possible. Hydrocortisone may be used to treat hypotension after other treatment has failed. |
BP: blood pressure; CV: conventional ventilation; CVP: central venous pressure; ECMO: extracorporeal membrane oxygenation; ETT: endotracheal tube; FiO2: fraction of inspired oxygen; GA: gestational age; IV: intra-venous; iNO: inhaled nitric oxide; HFOV: high-frequency oscillatory ventilation; LV: left ventricle; MAP: mean airway pressure; NaCl: sodium chloride; NIRS: near-infrared spectroscopy; SIMV: synchronized intermittent mandatory ventilation; SIPPV: synchronized intermittent positive pressure ventilation; PaO2: arterial partial pressure of oxygen; PaCO2: arterial partial pressure of carbon dioxide; PEEP: positive end expiratory pressure; PDA: patent ductus arteriosus; PH: pulmonary hypertension; PIP: peak inspiratory pressure; PVR: pulmonary vascular resistance; RDS: respiratory distress syndrome; RV: right ventricle.
The pathophysiology of pulmonary hypoplasia and CDH-PH often results in respiratory failure and hemodynamic instability beginning at birth. Therefore, cerebral oxygenation monitoring using near-infrared spectroscopy (NIRS) may serve as a valuable adjunct to pulse oximetry and heart rate monitoring, which currently guide resuscitation efforts per Neonatal Resuscitation Program guidelines. The use of NIRS from the delivery room is now implemented in some centers.35
Sedation and analgesia
Adequate sedation plays a critical role in reducing stress, decreasing oxygen consumption, and preventing patient-ventilator dyssynchrony.35,56,57 Additionally, patients with CDH-PH should be managed in a calm, noise-free environment, with minimal and gentle handling to reduce the risk of hypoxic episodes. Continuous opioid infusions are commonly employed, with benzodiazepines or dexmedetomidine added in certain cases to enhance sedation.35,41 While neuromuscular blocking agents may be considered in specific situations, such as severe CDH-PH or refractory hypoxemia, their use is generally reserved for critical scenarios, particularly during HFOV, as its use has been associated with increased mortality.35,58 Effective analgesia is required after surgical repair.59
Fluid management and nutrition
Careful fluid management is critical. Initial fluid intake needs to be restricted to prevent pulmonary edema.35,41,56,60 Diuretics may be used in selected cases.40 Parenteral nutrition should be initiated early, as enteral feeds are often delayed until after surgical repair and hemodynamic and respiratory stabilization.35,56,60 Once stable, minimal enteral feeding may be cautiously introduced to promote gut integrity.56,60
Antibiotics
Empirical broad-spectrum antibiotics (e.g., ampicillin and gentamicin) are started upon admission if there is any risk of bacterial perinatal infection, possible bowel ischemia, or risk deriving from the invasive procedures. Therapy is adjusted in accordance with the clinical course and culture results. Cefazolin may be used for perioperative antibiotic prophylaxis.61
Hemodynamic support
Newborns with CDH often present with compromised cardiac function.62 Ventricular dysfunction plays a key role in determining disease severity and mortality.63,64
The goal of hemodynamic management should be to ensure adequate end-organ perfusion, as assessed by heart rate, urine output, and lactate levels.41,65 Echocardiography is recommended whenever there are signs of poor perfusion or if blood pressure falls below the normal range for the gestational age, combined with a pre-ductal oxygen saturation under 80%. It can help to determine whether the poor perfusion is caused by hypovolemia or myocardial dysfunction.41
Currently, echocardiography plays a central role in the evaluation of infants with CDH, not only in the assessment of hypoxemic respiratory failure, but also as a key tool for early screening, phenotypic classification, and longitudinal monitoring of PH and cardiovascular dysfunction.5,66,67
Whenever feasible, a comprehensive baseline echocardiographic assessment should be performed prior to the initiation of cardiovascular therapies, allowing for accurate characterization of the predominant hemodynamic phenotype. This initial evaluation should include an assessment of PH severity, RV and LV systolic and diastolic function, ventricular interdependence, atrial and ductal shunting patterns, and the exclusion of associated congenital heart disease.5,66,67
Given the dynamic and frequently mixed nature of CDH-PH phenotypes, serial echocardiographic evaluations are essential to guide phenotype-directed therapy, monitor response to interventions, and detect evolving changes in cardiac function and pulmonary or systemic hemodynamics at the bedside.5,66–70
Echocardiographic assessment should be performed and interpreted by experienced pediatric cardiologists and/or neonatologists with expertise in functional echocardiography, ensuring an accurate incorporation of imaging findings into individualized clinical decision-making.69
Additionally, echocardiography helps to determine the appropriate timing of surgical repair. It is also essential for identifying candidates for ECMO and for monitoring postoperative cardiac function and pulmonary hemodynamics. Postoperatively, echocardiography is used to assess residual PH and ventricular performance. In severe cases, it also supports decisions regarding ECMO initiation, management, and weaning. Thus, echocardiography is an indispensable, non-invasive tool for the diagnosis, management, and longitudinal monitoring of the hemodynamic status in CDH patients.5,41,57,58,71–75
Hypovolemia requires correction through appropriate fluid administration.41 However, hypovolemia generally does not represent the primary cause of hemodynamic instability in CDH. Given the risk of both left and right ventricular dysfunction, fluid administration should be undertaken cautiously and guided by echocardiographic assessment.41
Due to the pathophysiology of CDH, structural pulmonary hypoplasia with a reduced pulmonary vascular bed, increased vascular muscularization, and heightened vasoreactivity, CDH-PH usually comprises varying degrees of both pre-capillary and post-capillary components. Accordingly, CDH-PH can be broadly categorized into three phenotypes.5,67,76 Phenotype 1 is characterized by mild or absent PH with a compliant RV, preserved biventricular function, and predominantly left-to-right shunting at both the ductal and atrial levels. Phenotype 2 represents mainly pre-capillary PH, with increased PVR and either preserved cardiac function, primary RV dysfunction, or secondary LV impairment due to ventricular interdependence, typically associated with predominant right-to-left shunting. Phenotype 3 corresponds to mainly post-capillary PH, driven by primary LV dysfunction with elevated left-sided filling pressures, and characterized by right-to-left ductal shunting with left-to-right atrial shunting. Importantly, these phenotypes should not be regarded as fixed entities; rather, they exist along a dynamic spectrum and may evolve over time, being significantly influenced by disease progression, cardiopulmonary interactions, and the initiation of vasoactive and pulmonary vasodilator therapies, which can modify both echocardiographic findings and shunt patterns.5,67,76
Some authors prefer to describe CDH-PH as associated with predominantly RV dysfunction (mainly pre-capillary), predominantly LV dysfunction (mainly post-capillary), or mild PH with no significant ventricular dysfunction, since these phenotypes are dynamic and may coexist, with one component being predominant.35
Accurate characterization of the underlying hemodynamic phenotype can be challenging, as pulmonary vasodilators (such as oxygen or iNO), positive inotropes, and non-specific vasopressors are often initiated before the first echocardiographic assessment, potentially modifying the baseline physiology. In addition, the spontaneous or therapeutic closure of the PDA, although uncommon, or the absence of an atrial-level communication may further complicate phenotypic classification. Heart–lung interactions are also an important consideration, as lung derecruitment or hyperinflation can significantly impact PVR and cardiac performance. Since these phenotypes are dynamic rather than static, the serial clinical and echocardiographic assessment of the hemodynamic effects of treatment may therefore provide valuable additional insights.5
When RV dysfunction associated with significant CDH-PH is the predominant presentation (phenotype 2; predominantly pre-capillary PH), management should primarily focus on reducing PVR, optimizing RV-pulmonary arterial coupling, and supporting RV function.35,67 Targeted pulmonary vasodilators such as iNO and milrinone are commonly used in this setting, alongside inotropic support when indicated. Milrinone, dobutamine, and low-dose epinephrine are generally the preferred agents for improving myocardial performance due to their more favorable pulmonary vascular profile.35,38,67 Systemic hypotension in this phenotype can also contribute to clinical deterioration, often reflecting RV dysfunction and impaired diastolic filling, with reduced coronary perfusion.67 Vasopressors may restore systemic pressure and coronary blood flow. Epinephrine, norepinephrine, or vasopressin are the preferred agents.67 Norepinephrine enhances diastolic pressure and coronary blood flow when LV function is preserved.67
Dopamine, a non-specific vasopressor with dose-dependent adrenergic effects, has historically been used in some centers to support systemic blood pressure. However, experimental and clinical data suggest that dopamine may increase PVR and worsen RV afterload, particularly in neonates with reactive pulmonary vasculature such as those with CDH. Therefore, dopamine is not recommended as first-line therapy in CDH patients with RV dysfunction and PH, and its use is increasingly discouraged.5,67,76–78 If considered, dopamine should be reserved for exceptional circumstances, administered at the lowest effective dose, and guided by close clinical and echocardiographic monitoring, while carefully weighing alternative agents with a more favorable hemodynamic profile.35,38
High doses of dopamine (> 15 mcg/kg/min) should be avoided, as they are associated with excessive systemic and pulmonary vasoconstriction, increased myocardial oxygen demand, and the potential worsening of global hemodynamics.35 The combination of dopamine with pulmonary vasodilators such as milrinone should be approached with caution, as dopamine-induced vasoconstriction may offset the beneficial pulmonary and lusitropic effects of milrinone.
Prostaglandin E1 (PGE1) is indicated when a dilated and dysfunctional RV is present in the setting of systemic or supra-systemic pulmonary arterial pressures and a restrictive or closing ductus arteriosus, as maintaining ductal patency may help unload the RV and support systemic perfusion.67,69
When LV dysfunction predominates (phenotype 3; predominantly post-capillary PH), management should aim to improve myocardial contractility, optimize preload, and reduce LV afterload. Low-dose epinephrine and dobutamine are commonly used in this setting.35,38,67 Low-dose epinephrine improves myocardial contractility and cardiac output, making it suitable for treating LV dysfunction and RV dysfunction in CDH. However, higher doses may lead to vasoconstriction, potentially increasing PVR and worsening PH.67 Milrinone may be beneficial due to its inotropic, lusitropic, and afterload-reducing effects; however, careful monitoring is required because of its potential to cause systemic hypotension.35,38 Low-dose dopamine may be used, although it is not the first choice and the potential to worsen pulmonary pressure should always be considered.35 In cases of systemic hypotension with preserved cardiac function, vasopressors with a more favorable pulmonary vascular profile are preferred, such as norepinephrine and epinephrine. Norepinephrine increases SVR and diastolic blood pressure and coronary perfusion while modestly improving pulmonary hemodynamics via α-2-mediated vasodilation.67 Nonetheless, norepinephrine may be used cautiously when cardiac function is adequate, acknowledging its potential to increase pulmonary arterial pressure.28 Vasopressin may be considered at low doses, as it predominantly increases SVR while relatively sparing the pulmonary circulation, although excessive afterload may further impair LV function.35,76,77 Vasopressin is generally reserved as rescue therapy for refractory hypotension; however, some centers have adopted it as a first-line vasopressor in selected cases. Also, vasopressin has minimal beneficial effects on PH.35,76,77 It should be administered cautiously and at low doses, as it may increase cardiac afterload and further impair LV function.76,77 Hydrocortisone should be considered in cases of vasopressor-refractory hypotension, particularly when relative adrenal insufficiency is suspected. Its use should be limited to short-term rescue therapy and guided by clinical response.79–89
Table 4 provides a summary of the effects of the vasoactive drugs used in treating CDH.5,28,35,38,41,62–65,67,69,72,73,75–95
Table 4. Summary of the effects and doses of vasoactive agents5,28,35,38,41,62–65,67,69,72,73,75–95
| Vasoactive agent | Effects and doses |
|---|---|
| Milrinone | Consider in cases with predominant RV dysfunction and severe PH (phenotype 2). Inotropic effects → improves RV contractility. Pulmonary vasodilator effects → reduces PVR, lowering RV afterload. Caution: may precipitate systemic hypotension. Consider also in cases with LV dysfunction/biventricular failure (phenotype 3). Loading dose: this is usually not used, as in neonates with CDH and hemodynamic instability it may worsen or cause hypotension, with the harmful effects outweighing the benefits. It can be used when systemic blood pressure is at the upper limit of normal. A loading dose achieves therapeutic levels faster: 50 mcg/kg over 15 minutes (in pre-term neonates < 30 weeks, with infusion over three hours). Maintenance infusion: initial dose: 0.2-0.33 µg/kg/min (minimizes risk of hypotension). Titration: can be gradually increased up to 0.66 µg/kg/min, and in some cases, up to 1.0 µg/kg/min if tolerated (monitor for BP and perfusion). In the case of milrinone-associated systemic hypotension, the combination with norepinephrine or epinephrine may be a good option, as it allows for an inotropic effect, pulmonary vasodilation, and BP to be maintained. The use of milrinone in patients with renal failure and oliguria demands caution due to the drug’s predominantly renal clearance and the increased risk of accumulation and toxicity, including hypotension, arrhythmias, and thrombocytopenia. |
| Dopamine | Non-selective vasoactive agent with dose-dependent adrenergic effects; historically used for systemic blood pressure support in neonates with CDH. Not recommended as first-line therapy in CDH associated with PH due to its potential to increase PVR and RV afterload. May be considered only in selected cases of systemic hypotension with impaired cardiac output, when alternative agents with a more favorable pulmonary vascular profile are unavailable or contraindicated. Effects on myocardial contractility and systemic vascular resistance are highly variable and unpredictable in critically ill neonates and should be guided by close clinical and echocardiographic monitoring. Dose-dependent effects (variable and overlapping): – 2-5 mcg/kg/min: dopaminergic effects on splanchnic and renal circulation (limited clinical relevance in CDH). – 5-10 mcg/kg/min: β1-adrenergic effects (variable inotropic response). – > 10 mcg/kg/min: α-adrenergic vasoconstriction with increased SVR and potential increase in PVR. Dosing considerations: suggested starting dose (if used): 3-5 mcg/kg/min; titrate cautiously, usually not exceeding 10-15 mcg/kg/min, based on systemic BP, markers of end-organ perfusion (lactate and urine output), and echocardiographic assessment. Avoid doses > 15mcg/kg/min, as they are associated with excessive systemic and pulmonary vasoconstriction, increased myocardial oxygen demand, and potential worsening of global hemodynamics. Dosage should be titrated according to the hemodynamic effect but not the standardized dosing regimen. |
| PGE1 | Prostaglandin E1 (PGE1) is reserved for specific situations, guided by echocardiographic findings. In CDH with severe PH, the RV may not be able to pump effectively into the high-resistance pulmonary circulation. PGE1 keeps the ductus arteriosus open, allowing right-to-left shunting through the ductus. This offloads the RV and allows systemic perfusion to be maintained via the ductus. This way, PGE1 may optimize shunting patterns temporarily, buying time for pulmonary vasodilators (like iNO) to take effect. Also, the indication for PGE1 in LV dysfunction is to maintain systemic perfusion in newborns whose circulation depends on a patent ductus arteriosus, providing temporary support until inotropic support is effective. It is also favored in infants with evidence of structural heart disease to maintain ductal patency. Side effects: apnea, hypotension, and fever. Initial dose: 0.01 mcg/kg/min. Maintenance range: 0.01-0.05 mcg/kg/min. Maximum dose: 0.1 mcg/kg/min. |
| Epinephrine | May be used in CDH patients: (1) to support myocardial contractility (inotropy), since both right and left ventricular dysfunction may occur; (2) to increase systemic BP (MAP); (3) in cases of severe cardiogenic shock or refractory hypotension. Starting dose: 0.01 mcg/kg/min; low dose: 0.01-0.05 mcg/kg/min (↑ inotropy and ↑ HR); moderate dose: 0.05-0.1 mcg/kg/min (↑ cardiac output and ↑ SVR); high dose: > 0.1 mcg/kg/min (vasoconstriction, ↑ SVR, and potential ↑ afterload) and should not be used in CDH-PH. Caution in CDH patients: increased afterload from high doses may worsen RV function or increase PH. Tachycardia and increased myocardial oxygen demand can be harmful. Always use echocardiography to guide use in the context of RV/LV performance and shunt direction. |
| Dobutamine | Increases myocardial contractility (positive inotrope). Improves cardiac output; especially useful in LV dysfunction. Improved LV output helps lower left atrial pressure, which can improve pulmonary venous drainage. Mild vasodilation (from beta-2 activity), which can help reduce afterload without significantly dropping BP. Initial dose: 2 to 5 mcg/kg/min. Titration: dose is usually increased in increments of 1-2 mcg/kg/min if the desired hemodynamic effect is not achieved, aiming for optimal cardiac output and BP. Maximum dose: 10 mcg/kg/min; higher doses may be used in some situations (under close monitoring), but the risk of tachycardia or arrhythmias increases. |
| Norepinephrine | This is sometimes used in the management of CDH, particularly in cases of severe hypotension, shock, or poor perfusion. It is a potent vasopressor that works by constricting blood vessels, thereby increasing SVR and MAP. Useful when cardiac output is normal but vasoconstriction is required. Usual dose: 0.05 to 0.1 mcg/kg/min. Titration: the dose can be gradually increased by increments of 0.05 mcg/kg/min depending on the clinical response (blood pressure, urine output, and overall perfusion). Maximum dose: while neonates can tolerate doses up to 1-2 mcg/kg/min, the goal is to use the lowest effective dose to maintain adequate perfusion and avoid excessive vasoconstriction. When norepinephrine doses exceed 0.5 mcg/kg/min in patients with CDH, hemodynamics should be reassessed and alternative vasopressors or inotropes considered (or ECMO), as further dose escalation offers limited benefit and increases the risk of excessive vasoconstriction and impaired microcirculatory perfusion. Can cause excessive peripheral vasoconstriction, renal ischemia, and arrhythmias/tachycardia. Norepinephrine should be used cautiously when FiO2 > 0.6, as its vasoconstrictive effect may increase PVR and worsen right-to-left shunting. Use should be guided by echocardiographic and perfusion parameters. |
| Hydrocortisone | Consider hydrocortisone if inadequate response from fluid resuscitation and inotropic support. Hydrocortisone can help improve vascular responsiveness to fluid management, thereby supporting BP and preventing hypertension from fluid overload. Its use in pre-term or critically ill neonates has been shown to improve cardiovascular stability, particularly in those with shock or hypotension. Loading dose: 1-2 mg/kg IV. Maintenance dose: 1 to 2 mg/kg/day in divided doses, every eight to 12 hours. Maximum dose: up to 3 mg/kg/day (in severe cases). High doses can lead to immunosuppression and hyperglycemia. Tapering: reduction of 25-50% every 24-48 hours, as the neonate stabilizes. |
| Vasopressin | Vasopressin is generally reserved as rescue therapy for refractory hypotension and PH unresponsive to catecholamines and iNO; however, some centers have adopted it as a first-line vasopressor in selected cases. Vasopressin has minimal beneficial effects on PH. Starting dose: 0.01-0.1 units/kg/h, started at the lowest dose and titrated based on BP response. Titration: dose may be increased gradually in increments of 0.01-0.05 units/kg/h if there is an insufficient response in MAP or perfusion. Maximum dose used in neonates is typically around 0.3 units/kg/h. |
BP: blood pressure; CDH: congenital diaphragmatic hernia; ECMO: extracorporeal membrane oxygenation; HR: heart rate; iNO: inhaled nitric oxide; LV: left ventricle; MAP: mean arterial pressure; PH: pulmonary hypertension; PVR: pulmonary vascular resistance; RV: right ventricle; SVR: systemic vascular resistance.
Management of pulmonary hypertension
CDH-PH is a major cause of morbidity and mortality in CDH.5,7 Echocardiographic evaluation is essential for diagnosis and monitoring.41,47 Although oxygen is a powerful pulmonary vasodilator, using concentrations greater than 50% has not demonstrated additional benefits for pulmonary vasodilation.93 In fact, studies have shown that hyperoxic ventilation can increase oxidative stress and lung injury, and may paradoxically reduce the vasodilatory response to iNO.93 iNO is the first-line therapy for PH, particularly in the presence of pre-capillary hypertension and right-to-left shunting across an atrial shunt and PDA, because it selectively dilates the pulmonary arterial vasculature, reducing PVR, improving blood flow through the lungs, enhancing oxygenation, and decreasing the magnitude of the shunt, all without causing systemic hypotension.41,94,95 iNO should be started when the oxygenation index (OI: mean airway pressure × FiO2/PaO2) is over 20 and/or the pre- and post-ductal saturation difference is greater than 10%.41 iNO should be postponed until LV function improves, because its pulmonary vasodilatory effect can increase pulmonary venous return to a compromised LV, potentially worsening existing LV dysfunction and causing systemic hypotension or pulmonary edema.96 iNO responders are defined by any of the following criteria: a 10-20% reduction in the pre- and post-ductal saturation difference, a 10-20% increase in PaO2, an improvement in hemodynamic parameters (e.g., a 10% rise in mean blood pressure), or a decrease in lactate levels.41 In non-responders, iNO should be discontinued.41 Sildenafil and/or prostacyclin analogs, as well as bosentan, may be used as adjuncts to vasoactive agents, particularly after milrinone.35 Intravenous sildenafil should be considered in severe CDH-PH.41 Sildenafil can be used both in acute situations, as an adjunct therapy when iNO and/or milrinone are insufficient, and in chronic use to maintain the pulmonary pressure reduction after stabilization.97–102 Bosentan, on the other hand, is generally reserved for chronic use in the postoperative period.101,102
Optimization of oxygenation, ventilation, and acid-base balance are also key components of management.80 Table 5 summarizes the mechanism of action and dosage of pulmonary vasodilator agents used in CDH-PH.35,41,67,80,93–102
Table 5. Mechanism of action and dosage of pulmonary vasodilator agents used in pulmonary hypertension associated with congenital diaphragmatic hernia35,41,67,80,93–102
| Agent | Effects and doses |
|---|---|
| Nitric oxide | Selective pulmonary vasodilator without causing systemic hypotension; helps to improve ventilation-perfusion matching and oxygenation. It is delivered via ventilator circuit as a continuous inhaled gas. Typical initial dose: 20 ppm; dose may be adjusted based on response and oxygenation. The focus is on titrating down once improvement occurs to minimize side effects. Doses above 20 ppm (up to 40 ppm) have not shown additional benefit and may increase the risk of side effects such as methemoglobinemia and NO2 toxicity. iNO should be part of a multimodal approach including optimal ventilation strategies. Needs careful monitoring of oxygenation (e.g., oxygenation index and arterial blood gases) and hemodynamics. Response may be variable in CDH patients because pulmonary hypoplasia limits the number of vessels available to vasodilate, and also due to the possibility of primary LV dysfunction in mixed phenotypes or those predominantly with post-capillary PH. Lack of response or rebound PH may occur; iNO is not universally effective in CDH. A negative response to iNO should prompt early echocardiography to rule out a primary left heart phenotype and weaning of treatment. Once oxygenation improves, gradual weaning of iNO is recommended to avoid rebound PH. |
| Sildenafil | Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor, which works by increasing the levels of cyclic-GMP within smooth muscle cells in the pulmonary vasculature. This leads to vasodilation and a reduction in PVR. It reduces right ventricular afterload, improving right ventricular function and cardiac output. It improves pulmonary blood flow, which leads to better ventilation–perfusion matching in the lungs. Sildenafil is often used in combination with other therapies, such as iNO or inotropes. It can also be used alongside mechanical ventilation or ECMO (if needed). It is indicated when other treatments like iNO or HFOV are either insufficient or require additional support. Starting oral dose: 0.25-0.5 mg/kg administered every six to eight hours. Maximum oral dose: 2 mg/kg every six hours. IV: 0.4 mg/kg loading dose over 3 h → infusion 1.6-2 mg/kg/day; omit loading if hypotensive. Careful monitoring of BP, heart rate, and oxygenation is essential during sildenafil therapy to avoid potential side effects, such as hypotension or bradycardia. Special considerations: pulmonary vasodilatory effects are not confined to well-ventilated portions of the lung, as in the case with iNO, which could contribute to a worsened V:Q mismatch. The duration of IV sildenafil therapy varies but is typically used for a short period while transitioning to oral sildenafil if ongoing treatment is required. Once the neonate stabilizes and the risk of PH decreases, the IV formulation can be transitioned to oral sildenafil at similar doses (around 0.25-1 mg/kg every six to eight hours). |
| Prostacyclin analogs | Prostacyclin analogs are used as part of advanced pulmonary vasodilator therapy, especially when iNO is insufficient or not effective. They act by vasodilation of pulmonary arteries and inhibiting smooth muscle proliferation. Reserved for severe or refractory PH. Often used in combination with other therapies like iNO, phosphodiesterase inhibitors (e.g., sildenafil), and ECMO. Iloprost (inhaled): can be used as an adjunct to iNO or when iNO response is limited; short half-life; multiple daily doses or continuous nebulization needed. Limited data in neonates but used off-label. Dose: 0.5-2 mcg/kg per inhalation, nebulized every two to three hours, six to nine times per day (due to short half-life ~30 minutes); some centers use continuous nebulization via ventilator circuit. Epoprostenol (IV): continuous IV infusion; potent vasodilator and inhibitor of platelet aggregation. Starting dose: 1-2 nanograms/kg/min; titration: increase by 1-2 ng/kg/min every 30-60 minutes based on response and tolerance; typical range: 7-10 ng/kg/min. Inhalation dose: 20-50 ng/kg/min. Treprostinil: available in IV, subcutaneous, and inhaled forms; less commonly used in neonates; more data in older children and adults; longer half-life than epoprostenol. IV starting dose: 1-2 ng/kg/min; titration: increase by 1-2 ng/kg/min every 12-24 hours; typical dose range: 5-20 ng/kg/min. |
| Bosentan | Bosentan, an oral endothelin receptor antagonist, blocks ET-A and ET-B receptors, reducing vasoconstriction and vascular proliferation. It is used in infants with CDH and PH to help lower PVR and improve long-term outcomes. It is typically part of a chronic management strategy, not for acute neonatal stabilization. Even after initial stabilization, some CDH survivors develop persistent or progressive PH that worsens over weeks to months. Sometimes used before discharge to support pulmonary transition. Oral: 0.5-2 mg/kg/dose, twice daily. Commence at 0.5 mg/kg/dose 12 hourly. Increase incrementally in consultation with cardiologist to a maximum of 2 mg/kg/dose 12 hourly. |
CDH: congenital diaphragmatic hernia; cGMP: cyclic guanosine monophosphate; iNO: inhaled nitric oxide; IV: intravenous; HFOV: high-frequency oscillatory ventilation; NO2: nitrogen dioxide; PH: pulmonary hypertension; ppm: parts per million; PVR: pulmonary vascular resistance.
Extracorporeal membrane oxygenation
If maximal medical management fails to stabilize oxygenation and/or hemodynamics, ECMO should be considered.41,103 The benefit of ECMO in the treatment of infants with CDH remains unclear.41 The ELSO Registry showed a survival rate of 51% of patients with CDH who required ECMO. ECMO seems to improve survival rates in CDH patients who are most severely affected, but the potential complications of ECMO delivery outweigh the benefit in patients who are less severely affected.102 Criteria typically include an OI > 40 for at least three hours despite maximal support, inability to maintain pre-ductal saturations > 85% or post-ductal saturations > 70%, increased PaCO2 and respiratory acidosis, peak inspiratory pressure ≥ 28 cmH2O, or mean airway pressure > 17 cmH2O required to achieve saturation > 85%, inadequate oxygen delivery with metabolic acidosis as measured by elevated lactate ≥ 5 mmol/L and pH, systemic hypotension, resistance to fluid and inotropic therapy, resulting in urine output or severe cardiovascular compromise that is unresponsive to inotropes.41 Venoarterial (VA) is often preferred over venovenous (VV) ECMO in infants with CDH due to the need for both respiratory and cardiac support. However, several studies comparing VA and VV ECMO in this population have not demonstrated a significant difference in mortality between the two modes. Given that VA and VV ECMO have similar outcomes, the choice should be based on institutional expertise.35 ECMO provides time for pulmonary vasculature and lung function to improve before surgical repair. Relative contraindications should be evaluated individually in consultation with the surgical, neonatology, and ECMO teams to assess eligibility. These include a birth weight under 1.7-2 kg, gestational age under 32 weeks, significant congenital or chromosomal anomalies, and complex congenital heart disease, especially those involving single-ventricle physiology. Intracranial hemorrhage of grade III or higher is generally considered an absolute contraindication.35
Surgical repair
Surgical repair plays a crucial role in the management of CDH, aiming to restore the normal anatomy by repositioning herniated abdominal organs into the abdomen and closing the diaphragmatic defect. Surgery is not an emergency procedure and should be performed only after the infant is stabilized. Cardiac dysfunction is common in CDH and has a significant impact on morbidity and mortality.70 Stabilization for surgery should be considered in the presence of clinical, blood gas, and echocardiographic criteria: a normal mean arterial pressure for the gestational age (> 3rd centile), pre-ductal oxygen saturation of 85-95% on FiO2 ≤ 50% (tolerating ≤ 60%), lactate level < 3 mmol/L, and urine output > 2 mL/kg/h, tolerance of nursing care without instability and with adequate sedation, arterial pH > 7.25, PaCO2 < 60 mmHg (pre-ductal) or < 65 mmHg (post-ductal), stable ventilation settings, normal biventricular function on stable inotropes (if needed), PDA shunt > 50% left-to-right, pulmonary pressures that are stable or not worsening, and stability on serial echocardiograms (≥ 2) at least 24 hours apart.9,35,41,70 The assessment, including the aforementioned parameters, should be performed daily during the preoperative period, and once this window of clinical stability is achieved, surgery should be carried out within 24 hours.70 Unlike ventricular function, we should not expect or require the normalization of pulmonary arterial pressure/PH prior to surgical repair.70 Indeed, the optimal repair window includes some degree of stable PH or PH that is not worsening.70 Given the close association of heart function and outcomes of CDH, cardiotropic medications, when needed, should not be discontinued prior to operative repair.70
In CDH patients on ECLS, normalization of LV function is required as a criterion for surgical repair or decannulation for surgery. Due to RV unloading by the ECMO cannula, mild-to-moderate RV dysfunction may persist and should not delay surgery.70
To enhance understanding of echocardiographic assessment in determining the optimal timing for surgery, reading the article by Wren JT et al.70 is recommended.
In infants with no evidence of liver herniation, requiring minimal ventilatory support, and with no significant evidence of CDH-PH or pulmonary hypoplasia, surgical repair can be performed on the second or third day of life.35 In infants with moderate-to-severe pulmonary hypoplasia and CDH-PH, surgical repair is often delayed. Although most of these infants initially exhibit clinical instability, they typically demonstrate subsequent improvement and stabilization, allowing surgical repair to be performed around days five to ten of life.35 The timing and approach of the repair, whether open or minimally invasive, are determined based on the patient’s clinical status and institutional protocols. Depending on the infrastructure and clinical protocols of the unit, CDH repair can be performed at the infant’s bedside. This approach may reduce the risks associated with transporting a hemodynamically unstable neonate who requires extensive supportive equipment and continuous monitoring.35 Repair can be performed while the patient is on ECMO.35,41
Chronic lung disease
The definition of CLD in infants with CDH has traditionally followed that used for preterm infants with bronchopulmonary dysplasia, based on oxygen dependency at 28-30 days of life. However, due to the different pathophysiology, a more appropriate definition for CLD in CDH may be oxygen dependency 30 days after surgical repair. Studies show this is linked to important clinical outcomes, such as reduced lung function and increased respiratory and developmental morbidity. Respiratory management should be individualized, considering the heterogeneity of lung involvement and the high prevalence of CDH-PH in these infants. Strategies like careful PEEP use, adjusting respiratory rate and expiratory time, and bronchodilator therapy may be beneficial. Importantly, lung growth continues throughout childhood.35
Sildenafil and bosentan can be considered for the treatment of PH in postoperative patients with CLD, although the evidence in the literature remains limited.98 Their use in CDH patients requires careful monitoring of pulmonary, cardiac, and hepatic function due to potential complications and drug interactions. The choice of treatment should be individualized, considering the severity of PH, comorbidities, and the patient’s post-surgical recovery status. Close follow-up, including a pediatric cardiologist and a pulmonologist, is essential to ensure efficacy and to minimize adverse effects.101,102
Malnutrition and feeding difficulties
Malnutrition and feeding difficulties are common in infants with CDH and often persist into early childhood. Enteral feeds can be commenced within 24 hours of surgery, after discussion with the surgical team. Intestinal ileus and reflux are common and continuous feeds (gastric or transpyloric) may be required in the first few days (Table 6).35,103–105
Table 6. Nutritional approach to infants with congenital diaphragmatic hernia35,103–105
| Aspect | Key points/recommendations |
|---|---|
| Nutritional risk | Malnutrition and feeding difficulties are common in infants with CDH; early recognition of growth failure is essential. |
| Fluid management | Initial fluids: 60-80 mL/kg/day. Management should be restrictive. Before surgical repair, fluid progression should be cautious and always guided by the infant’s hemodynamic and respiratory status, to avoid pulmonary edema and the worsening of PH and cardiac function. Fluids are increased gradually as the infant stabilizes hemodynamically and metabolically. Gradual increase progressed by 10-20 mL/kg/day up to 120-150 mL/kg/day after stabilization. Monitor urine output (1-3 mL/kg/h), weight, electrolytes, and signs of fluid retention or pulmonary congestion. |
| Caloric requirements | Start at 40-60 kcal/kg/day and increase as possible up to 100-110 kcal/kg/day. To reduce failure to thrive and promote growth, once enteral feedings are tolerated, caloric intake should aim for 120-140 kcal/kg/day; target daily weight gain should be comparable to other term infants. |
| Protein | Start at 1.5-2 g/kg/day; progress to 3 g/kg/day to prevent catabolism. |
| Glucose | Start at 4-6 mg/kg/min; may increase to 8-10 mg/kg/min. Maintain blood glucose 70-120 mg/dL. |
| Lipids | Start at 0.5-1 g/kg/day; increase up to 3 g/kg/day (30-40% of total calories). |
| Parenteral nutrition (PN) | Initiation in the first 24 hours of life; monitor electrolytes, fluid balance, and metabolic parameters until enteral feeding can be introduced. Infants who require prolonged PN are at high risk of developing PN-associated cholestasis (conjugated bilirubin 1.5-2.0 mg/dL). In cholestasis lipid intake from pure soybean oil emulsions should be reduced to around 1 g/kg/day or replaced with mixed or fish oil-based emulsions (such as SMOFlipid or Omegaven), which can usually be administered at standard doses because they are less likely to induce or worsen cholestasis. In patients on ECMO, augment fluid removal with diuretic or continuous renal replacement therapy to maintain nutritional goals. |
| Enteral nutrition (EN) initiation | EN should be initiated only after surgical repair, once the infant is hemodynamically and respiratory stable and shows signs of intestinal readiness (bowel sounds, minimal gastric output, and absence of bilious drainage), according to the surgeon’s indication. It can also be initiated in infants on ECMO. NOTE: The presence of low-dose, weaning vasoactive support is not an absolute contraindication to initiating EN, provided perfusion is adequate (normal lactate levels and urine output). Small trophic feeds with breast milk can usually be started 48-72 hours postoperatively and progressed gradually as tolerated. |
| Feeding method | There is no clear evidence to support initiation with bolus versus continuous enteral feedings. The method of enteral feeding should be individualized based on hemodynamic stability, risk of aspiration, and intestinal function. Low-risk patients who are hemodynamically stable with adequate gastric motility and low aspiration risk are likely to tolerate bolus feeding: a bolus should be administered slowly (10-15 minutes) at small volumes (10-20 mL/kg per dose) every two to three hours, with gradual progression according to tolerance. Early trophic feeding, even in small amounts, is encouraged to stimulate intestinal maturation and reduce parenteral nutrition-associated cholestasis. High-risk unstable neonates, those on low-dose vasoactive support, or cases of postoperative gastric dysmotility may benefit from continuous feeding. Transpyloric feeding, delivered continuously, is reserved for patients with high aspiration risk or severe gastric intolerance/gastroparesis. Oral feeding by breast or bottle should begin at < 2 liters per minute respiratory support, in the absence of any contraindication to oral feeding. Preventive anti-reflux therapy (e.g., omeprazole) should not be started alongside enteral feeding in all patients, unless esophagitis is documented. The benefits of reducing gastric acid secretion in reflux treatment must be weighed against the associated risks. Also, preventive anti-reflux surgery at the time of CDH repair should not be routinely performed. |
| Milk choice | Breast milk preferred; if unavailable, term formula. In the case of intolerance: transpyloric feeding or hydrolyzed formulas. May require fortification, modular diets, or high-calorie formulas, as guided by a nutrition specialist. |
| Transition from PN to EN | Vulnerable period; may result in temporary calorie and protein deficits. Overlaps with weaning from respiratory support and sedation; prolonged in CDH due to feeding intolerance. |
| Weight gain goals | Gradual and individualized. Target weight gain should be comparable to other term infants (25-35 g/day) after EN initiation. Weight maintenance or 5-10% loss expected during PN. Ensure growth reflects lean body mass; monitor length and head circumference. |
| Monitoring | Daily weight, growth curve, tolerance, vomiting, abdominal distension, gastric residuals, and signs of malnutrition. In cholestasis, monitor liver enzymes (AST and ALT), GGT, and bilirubin levels. Long-term multidisciplinary nutritional support often required. Feeding support by pediatric occupational and speech therapists is an important component of outpatient management and should be available for infants who are not taking full oral feeds at discharge. The potential risk and benefit of home nasogastric and gastric tube should be carefully weighed for each individual patient. |
CDH: congenital diaphragmatic hernia; ECMO: extracorporeal membrane oxygenation; PH: pulmonary hypertension.
Implementing strategies such as human milk feeding, early recognition of growth failure, and earlier initiation of higher-calorie feeds is paramount. The transition from parenteral to enteral nutrition is a vulnerable period for calorie deficits and is often prolonged due to feeding intolerance. In some patients, surgical complications such as traumatic chylothorax and diaphragmatic paresis further exacerbate these feeding challenges.106–108
In cases of gastroesophageal reflux, non-pharmacological measures such as upright positioning, small frequent feeds, and slow feeding techniques should be prioritized, while pharmacological therapy with proton pump inhibitors or prokinetic agents may be considered when there is documented esophagitis, when symptoms persist, or when complications arise. Gastroesophageal reflux must be adequately managed through medical or surgical interventions.109
Feeding guidelines recommend starting with human milk and adjusting feeding progress based on tolerance. A hypercaloric diet may be necessary for selected patients, and a specialized nutritional plan should be individualized. Continuous monitoring by a dietitian is essential to support growth and meet nutritional goals.35,110,111
Outcomes in congenital diaphragmatic hernia
The prognosis of infants with CDH has improved over recent decades due to advances in perinatal care, surgical techniques, and neonatal intensive care. However, CDH continues to be associated with significant morbidity and mortality, particularly in cases involving severe pulmonary hypoplasia and CDH-PH.111
Infants with CDH are at risk for a wide range of complications that span multiple organ systems.111,112 Respiratory complications are among the most frequent and severe, including pulmonary hypoplasia, persistent CDH-PH, CLD, recurrent respiratory infections, and prolonged dependence on supplemental oxygen or mechanical ventilation. Nutritional and gastrointestinal problems are also common, with feeding difficulties, gastroesophageal reflux disease, malnutrition, growth failure, and feeding intolerance with frequent vomiting frequently reported. Cardiac complications may occur due to cardiac displacement and the presence of associated congenital heart defects, which are identified in up to 40% of cases. Neurological and developmental outcomes may be affected, as neurodevelopmental delays, neuromuscular hypotonia, and mild-to-moderate cognitive or motor impairments are frequently observed. Sensory impairments, such as hearing and visual deficits, can also occur. Surgical complications include hernia recurrence, surgical wound infections, prosthetic mesh-related problems, diaphragmatic paresis, and chylothorax. In addition, musculoskeletal abnormalities such as scoliosis and pectus excavatum may develop over time, often as a result of thoracic deformities or prolonged respiratory support.113,114
Overall, the management of CDH requires a multidisciplinary approach, with long-term follow-up to address the complex interplay between respiratory, nutritional, cardiac, neurological, and musculoskeletal sequelae.111–113
Survival rates vary widely and depend on several factors, including the size and side of the hernia, the presence of liver herniation, the degree of lung underdevelopment, and the need for ECMO. Overall survival in high-resource settings ranges from 60 to 80%, but may be lower in severe cases or in the presence of associated anomalies.114
In summary, while survival rates for CDH have improved, affected infants remain at high risk for multiple complications. A multidisciplinary approach and long-term follow-up are critical to managing the complex needs of these patients and improving quality of life. Even in cases with favorable short-term outcomes, long-term morbidity is common and may significantly affect quality of life.112,115
Conclusion
The treatment of neonates with CDH is complex and requires an individualized, multidisciplinary approach. Advances in perinatal management, gentle ventilation, hemodynamic support, and the selective use of ECMO have contributed to improved outcomes. Continued research and standardized protocols are essential to optimize survival and long-term quality of life in this vulnerable population.
Author contributions
The author was solely responsible for all aspects of the study and manuscript preparation.
Funding
None.
Conflicts of interest
None.
Ethical considerations
Protection of human subjects and animals. The authors declare that no experiments on humans or animals were performed for this research.
Confidentiality, informed consent, and ethical approval. This study does not involve personal patient data, medical records, or biological samples, and does not require ethical approval. SAGER guidelines do not apply.
Declaration on the use of artificial intelligence. The authors declare that no generative artificial intelligence was used in the writing or creation of the content of this manuscript.
